title: Homozygous deletion in TUSC3 causing syndromic intellectual disability: a new patient.
abstract: Defects in the TUSC3 gene have been identified in individuals with nonsyndromic autosomal recessive intellectual disability (ARID), due to either point mutations or intragenic deletions. We report on a boy with a homozygous microdeletion 8p22, sizing 203 kb, encompassing the first exon of the TUSC3 gene, detected by SNP-array analysis (Human Gene Chip 6.0; Affymetrix). Both nonconsanguineous parents come from a small Sicilian village and were heterozygous carriers of the microdeletion. The propositus had a few dysmorphic features and a moderate cognitive impairment. Verbal communication was impaired, with an inappropriate phonetic inventory, important phono-articolatory distortions, and bucco-phonatory dyspraxia. Comprehension was possible for simple sentences. Behavior was characterized by motor instability, high tendency to irritability and distraibility, anxiety traits, and an oppositional-defiant disorder. His parents were of normal intelligence. TUSC3 is thought to encode a subunit of the endoplasmic reticulum-bound oligosaccharyltranferase complex that catalyzes a pivotal step in the protein N-glycosylation process. TUSC3 has been recently reported as a member of the plasma membrane Mg(2+) transport system, with a possible involvement in learning abilities, working memory and short- and long-term memory. This is the third family in which a deletion has been described. Although the pathogenic mechanism has not been clarified yet, our report argues for a more prominent role of TUSC3 in the etiology of intellectual disability and that deletions encompassing this gene could be more common than expected.
authors.affiliation: Mendel Laboratory, IRCCS Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo (FG), Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Loddo
authors.forename: Valentina
authors.initials: V
authors.lastname: Parisi
authors.forename: Viola
authors.initials: V
authors.lastname: Doccini
authors.forename: Tiziana
authors.initials: T
authors.lastname: Filippi
authors.forename: Laura
authors.initials: L
authors.lastname: Bernardini
authors.forename: Paola
authors.initials: P
authors.lastname: Brovedani
authors.forename: Federica
authors.initials: F
authors.lastname: Ricci
authors.forename: Antonio
authors.initials: A
authors.lastname: Novelli
authors.forename: Agatino
authors.initials: A
authors.lastname: Battaglia
mesh_terms: D002648:Child; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D010641:Phenotype; D017384:Sequence Deletion; D013577:Syndrome; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C524338:TUSC3 protein, human; D025521:Tumor Suppressor Proteins
keywords: SNP-array; TUSC3 gene; autosomic recessive mental retardation (ARMR); homozygous 8p22 deletion; intellectual disability